**1. Introduction**

Vaccines have saved countless human lives from lethal infections since the modern use of vaccinia against smallpox by British physician Edward Jenner in the late eighteenth century and are today playing more and more crucial roles in fighting life-threatening diseases, of which, due to great advances made in branches of the field and related fields such as immunology and biotechnology, the scope has enormously expanded, ranging from the earlier aim of microorganism infections to the novel targets of autoimmune disorders, allergic reactions, and even malicious cancers [1]. However, the list of infectious diseases for which vaccines are urgently needed but do not yet exist is till long and in particular many pathogens such as HIV (human immunodeficiency virus), HSV (herpes simplex virus), and HCV (hepatitis C virus), showing on their surface elusive or ever changing immunogenic features to continuously dismantle a variety of potential arsenals; let alone numerous malignant tumors, autoimmune disorders such as multiple sclerosis, diabetes, and rheumatoid arthritis, which are all aggressively threatening human health and life, posing a big challenge to developing effective vaccines or immunotherapy [2].

response of recipients to the Ags, or change the type of immune responses; otherwise, subunit vaccines are engineered with functional carriers to form a vaccine adjuvant-delivery system (VADS), which is frequently made of a range of NPs (nanoparticles) using various materials capable of targeting the professional Ag-presenting cells (APCs) such as dendritic cells (DCs) and macrophages (MPs) to boost enormously the immunostimulatory activity of a vaccine

Polymeric Nanoparticles Engineered as a Vaccine Adjuvant-Delivery System

http://dx.doi.org/10.5772/intechopen.81084

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This chapter elaborates the material basis, formulation, rationale, and the state-of-the-art advances in the development of a VADS constructed with polymeric NPs which are made of certain crucial types of polymers such as PLGA, HA, polystyrene, or VLPs, which possess many beneficial features for eliciting immunity against a range of diseases. Thus, this comprehensive introduction will provide a useful reference to interested readers who may thus be attracted to denote their innovative talents to the development of vaccines based on VADS

Polymeric NPs, namely NPs made of highly biocompatible polymers, such as polystyrene, PLGA, proteins, chitosan, and hyaluronic acid (HA), have recently been widely explored as a DDS (drug delivery system) as well as VADS and show many excellent properties beneficial for therapeutic delivery of agents, for example, high stability can shelter the loaded Ags from environmental detriment and in vivo unwanted degradation; biocompatibility can reduce toxicity to recipients and their compliance; ease in modulation of particle size, surface charge, and specific binding characteristics allow developing multifunctional VADS [3, 4]. Thus, through fulfilling multiple functions, polymeric NPs are able to improve the efficacy of vaccines, for example, they can form a depot to enhance vaccine efficacy via elongated release and exposure of Ag at the site of injection; they can targetedly deliver vaccines to APCs promoting cellular uptake of Ags and thus enhancing Ag stimulation efficiency; they can alter intracellular process of Ags adapting immune responses toward the beneficial humoral and/ or cellular pathways; and also they can provide diverse administration routes for vaccination

to elicit the desired immunity at circulation system as well as mucosal sites [6, 11].

Although polymers suitable for constructing VADSs are usually thought to be biodegradable one since they cause no size-limited excretion and associated toxicity concern, certain nonbiodegradable materials possessing certain specific properties, such as chemical inertness and ease for fabricating stable NPs, are also the preferred candidates by researchers for engineering the kind of NPs with an accurate size and special shape, so as to be employed reliably to investigate these physical properties on the immune system and immune responses. For example, Plebanski and coworkers using nonbiodegradable polystyrene NPs performed studies on VADS and showed that polystyrene NPs loaded with OVA epitopes induced different immune responses in a size-dependent manner needing no additional adjuvant, and

and is thus making full use of Ags [6–10].

constructed, probably, with polymers.

**2.1. Polystyrene NPs as a VADS**

**2. Different polymeric NPs designed as a VADS**

Vaccines function against diseases through stimulating the host immune system with the antigenic components featured by pathogens or neoplasms to establish the antigen-specific immunity which is able to clear the abnormalities bearing the identical antigens. Vaccines developed for handling infectious diseases are mostly manufactured using the live attenuated or killed whole microbes, which have a high potency in triggering immune system but are argued to be associated with possible reversion to virulence due to mutation of administered strains, as evidenced by gene sequencing in vaccinated sufferers, thus causing safety concern. As many mechanisms underlying immunoresponses are revealed and great achievements are made in relevant fields, subunit vaccines, which are formulated with defined components including Ags to induce immunoresponses accurately targeting the matched objects thus causing few safety concerns, are now more and more employed to fight not only infectious pathogens but also other illnesses, providing, in particular, outstanding ways to overcome the previously intractable diseases, such as cancer [3]. Compared to conventional whole microbe vaccines, subunit vaccines possess many distinct properties which are beneficial for clinical applications, summarily including high safety profile, production needing no dangerous microorganisms, no redundant components to cause allergic or autoimmune responses, diverse usage including anticancer, and high capacity for several peptide epitopes targeting different stages in the life cycle or subtypes of a pathogen [4].

However, subunit vaccines are often weak immunostimulatory products, due to lack of such components as the pathogen-associated molecular patterns (PAMPs), which are expressed on a microbe surfaces and are able to activate the pattern recognition receptors (PRRs), such as the TLRs (toll-like receptors), NOD-like receptors (the nucleotide-binding oligomerization domain-like receptors), RIG-I-like receptors (retinoic-acid-inducible gene-I-like receptor), and C-type lectin receptors, thus facilitating host immunoresponses [5]. As such, subunit vaccines are often formulated with an adjuvant, which is a nonspecific immunopotentiating substance able to elevate, either in advance or simultaneously with the vaccine Ags, the immune response of recipients to the Ags, or change the type of immune responses; otherwise, subunit vaccines are engineered with functional carriers to form a vaccine adjuvant-delivery system (VADS), which is frequently made of a range of NPs (nanoparticles) using various materials capable of targeting the professional Ag-presenting cells (APCs) such as dendritic cells (DCs) and macrophages (MPs) to boost enormously the immunostimulatory activity of a vaccine and is thus making full use of Ags [6–10].

This chapter elaborates the material basis, formulation, rationale, and the state-of-the-art advances in the development of a VADS constructed with polymeric NPs which are made of certain crucial types of polymers such as PLGA, HA, polystyrene, or VLPs, which possess many beneficial features for eliciting immunity against a range of diseases. Thus, this comprehensive introduction will provide a useful reference to interested readers who may thus be attracted to denote their innovative talents to the development of vaccines based on VADS constructed, probably, with polymers.
